Steroid hormones are vital constituents for the proper functioning of the human body and can be classified into five groups based on the receptors to which they bind, namely: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens. It is known that steroid hormones aid in regulating metabolism, regulating water and salt function, regulating immune function, controlling inflammation, and developing sexual characteristics.
Despite their wide ranging biological activity, steroid hormones are difficult to deliver to a subject experiencing a disease or disorder where additional steroid hormone could help treat the disease or disorder. Progesterone, for example, has extremely poor oral bioavailability due to its limited water solubility. As a result, when given orally, it must be administered in a sufficiently high dose to obtain the desired pharmacokinetic profile. Higher dosages, however, are inherently less desirable as the greater the quantity dosed, the greater the risk that additional drug, beyond what the patient requires, could enter the bloodstream.
Progesterone is a naturally occurring C-21 steroid hormone belonging to the progestogen class. It is produced by the cells of the corpus luteum during the post-ovulatory luteal phase and to a lesser degree by the adrenal glands and the placenta during the second part of pregnancy. In women, progesterone levels are relatively low during the pre-ovulatory phase of the menstrual cycle, rise after ovulation, and are elevated during the luteal phase. Progesterone is commonly referred to as the “hormone of pregnancy” as it plays an important role in fetal development. Further, progesterone insufficiency can lead to premenstrual syndromes and menstrual irregularities.
Progesterone is used to support pregnancy in Assisted Reproductive Technology
(ART) cycles, to control persistent ovulatory bleeding, to prepare the uterine lining in infertility therapy, and to support early pregnancy. Further, progesterone can be used for regularizing menstruation.
Progesterone is also used to oppose uterine hyperplasia and uterine cancer in women who are treating the symptoms of menopause with estrogen therapies.
Because progesterone does not dissolve in water and is poorly absorbed, currently marketed oral progesterone dosage forms administered to patients result in both intra- and inter-patient variability. To overcome the drawbacks of poor bioavailability associated with natural progesterone, researchers have used various synthetic progesterone derivatives such as medroxyprogesterone, norethisterone, methylestrenolone, chlormadinone acetate, 6-dehydroretroprogesterone, and lynestrenol. But, use of these derivatives is associated with side-effects not associated with natural progesterone.